Heart failure is a chronic cardiac condition characterized by a deficiency in the ability of the heart to pump blood. Decreased cardiac output to the systemic circulation typically increases venous blood pressure, which often leads to blood backing up in the lungs. Low cardiac output also results in decreased blood perfusion to organs, such as the liver, kidney, brain, and heart itself. Over time, the effects of heart failure contribute to a worsening of the condition. Reduced blood supply to the heart causes less effective contraction of the heart. At the same time, higher venous blood pressure increases the heart preload. To compensate, the heart attempts to increase output by increasing muscle strength, which leads to myocardial hypertrophy (enlargement of the heart with thickening and stiffening of the heart wall). These conditions in turn lead to reduced cardiac output, resulting in a vicious cycle.
There are primarily two types of heart failure, systolic heart failure and diastolic heart failure. Systolic heart failure is characterized by a deficiency in systolic heart function, which causes insufficient expulsion of blood during systole. Diastolic heart failure is characterized by a deficiency in diastolic heart function, which causes insufficient ventricular filling during diastole.
Treatment for heart failure varies with the severity of the disease. Moderate heart failure is generally treated with lifestyle changes and medication, such as diuretics, digitalis, ACE inhibitors, and beta-blockers. Heart failure is also sometimes treated with cardiac resynchronization therapy (CRT) by implanting a biventricular pacemaker to synchronize the beating activity of both sides of the heart. CRT may be combined with implantable cardioverter-defibrillator (ICD) therapy. Severe heart failure may be treated with a heart transplant, a temporary artificial heart, or a ventricular assist device (VAD). A VAD is a blood pump designed to assist or replace the function of either one or both ventricles of the heart, on a short-term basis. VADs include right ventricular assist devices (RVAD), left ventricular assist devices (LVAD), and biventricular assist devices (BVAD). VADs may be either external or implantable.
An intra-aortic balloon pump (IABP) is sometimes used on a short-term basis for patients awaiting a heart transplant, or for patients recovering from open-heart surgery, also on a short-term basis. An IABP is a balloon that is generally placed in the aorta of a patient, and is inflated during diastole and deflated during systole, so as to reduce left ventricular preload and afterload. For example, U.S. Pat. No. 6,468,200 to Fischi, which is incorporated herein by reference, describes an IABP including a multiple-chamber balloon disposed at the distal portion of a catheter.
Counterpulsation is a technique for assisting the circulation by decreasing the afterload of the left ventricle and augmenting the diastolic pressure. Devices for achieving counterpulsation include intra-aortic balloons, pumping devices implantable in the chest, and external devices that apply a negative pressure to the lower extremities during cardiac systole. Counterpulsation devices are typically synchronized with a patient's cardiac cycle to apply pressure to blood vessels of the patient during diastole, and to remove the applied pressure immediately prior to systole, so as to increase stroke volume by decreasing afterload, to reduce heart workload, and to maintain or increase coronary perfusion. Counterpulsation techniques have been studied since the mid-1950s. Birtwell W C et al., in “The evolution of counterpulsation techniques,” Med. Instrum. 10:217-223 (1976), which is incorporated herein by reference, review the history of various counterpulsation techniques. Clauss R H et al., in “Assisted Circulation: 1. The Arterial Counterpulsator,” Journal of Thoracic and Cardiovascular Surgery 41:447 (1961), which is incorporated herein by reference, describe a pump placed on the arterial side of the circulation and used to alter the pressure of the left intraventricular aortic and arterial pulses. Unger F et al., in “The Windkesselventricle with guiding balloon as a new approach to assisted circulation,” Med. Instrum. 10:256-259 (1976), which is incorporated herein by reference, describe the implantation of balloons in aortas of dogs and a method for pneumatically driving the balloons synchronously with electrocardiogram (ECG) measurements, so as to increase hemodynamic efficiency.
Externally-applied counterpulsation devices are described, for example, in U.S. Pat. Nos. 5,554,103 and 5,997,540 to Zheng et al., and U.S. Pat. No. 3,866,604 to Curless et al., all of which are incorporated herein by reference. U.S. Pat. No. 5,514,079 to Dillon, which is incorporated herein by reference, describes techniques for improving circulation by applying external positive regional pressure on an extremity synchronously with the patient's heartbeat. An adjustable timing cycle is initiated at the QRS complex of the arterial pulse cycle. US Patent Application Publication 2002/0173735 to Lewis, which is incorporated herein by reference, describes a medical device for non-invasive counterpulsation treatment of heart disease and circulatory disorders through external cardiac assistance. The device comprises cuffs which are affixed on a patient's lower body and extremities, and which constrict by electromechanical activation, thereby augmenting blood pressure for treatment purposes.
US Patent Application Publication 2002/0173693 to Landesberg, which is incorporated herein by reference, describes a system for assisting a failing ventricle, which utilizes a single blood displacement chamber and a single cannula. The cannula is inserted into the failing ventricle cavity and is connected to a blood displacement actuator. The device is described as producing blood displacement at a critical time for a critical duration and with blood flow time course such that it improves the systolic function of the heart, augments cardiac output, and increases the generated pressure. The device is also described as improving diastolic function by increasing the ventricle compliance and imposing rapid relaxation of the ventricle wall. The device is described as providing additional external work without deteriorating the mechanical function of the failing ventricle, moreover it is described as decreasing the energy consumption of the failing heart and improving coronary perfusion. Consequently, the device is described as improving the balance between the energy supply (coronary perfusion) to the ventricle wall and the mechanical demands, and to thereby allow recovery of the failing heart.
U.S. Pat. Nos. 6,673,043, 6,406,422, and 6,511,413, also to Landesberg, describe related techniques to those described in the above-cited US Patent Application Publication 2002/0173693. These patents are incorporated herein by reference, as well.
PCT Publication WO 02/24254A2 to Khaghani et al., which is incorporated herein by reference, describes a blood circulation assistance device for location around a blood conduit. The device comprises an inflatable bladder for compressing the blood conduit to provide counterpulsation, and a pump for contracting and expanding the bladder. The pump expands the bladder at diastole, as determined by monitoring the cardiac cycle. An outer cuff surrounds the bladder in order to provide an outer limiting extent to the movement of the bladder.
U.S. Pat. No. 4,938,766 to Jarvik, which is incorporated herein by reference, describes implantable prosthetic devices and methods of use for increasing blood flow by increasing arterial compliance and reducing the magnitude of the pressure pulsations in the arterial system, and to increase perfusion of specific organs in order to overcome the deleterious effects of cardiovascular disease.
U.S. Pat. No. 6,030,336 to Franchi, which is incorporated herein by reference, describes a pump comprising variable volume means inserted in an artery, in particular, the descending aorta, enabling the volume through which the blood flows in this location to be modified cyclically and in a controlled manner. The device comprises a deformable enclosure in fluid communication with the variable volume. The variable volume and a spring coil urge the deformable enclosure against an increase of volume resulting from a pressure increase in the variable volume, and in the corresponding enclosure, so as to produce additional elastance for the artery during the heart cycle. In addition, an electric motor can control the deformable enclosure to increase or decrease its volume, and can exert its force in addition to or in subtraction from the force of the spring coil during the systolic and diastolic phases of the heart cycle.
U.S. Pat. No. 6,450,942 and European Patent Application 1 078 649 A1 to Lapanashvili et al., which are incorporated herein by reference, describe a technique for reducing heart load by measuring heart rhythm, and producing pressure pulsations in the peripheral vascular system in synchronization with the heart rhythm in a counterpulsation mode, so as to reduce pulse rate and/or systolic pressure, and thereby heart load.
U.S. Pat. Nos. 6,200,260, 6,299,575, and 6,428,464 to Bolling; U.S. Pat. Nos. 6,387,037, 6,390,969, and 6,685,621 to Bolling et al.; and US Patent Application 2003/0088147 to Bolling et al., all of which are incorporated herein by reference, describe an extracardiac pumping system comprising a pump implanted subcutaneously at a patient's groin. The pump draws blood from the patient's femoral artery and discharges blood to a peripheral artery that stems from the patient's aortic arch. The pump may be operated continuously or in a pulsatile fashion, synchronous with the patient's heart, thereby potentially reducing the pumping load on the heart.
U.S. Pat. No. 6,132,363 to Freed et al., which is incorporated herein by reference, describes a left ventricular-assist device comprising an inflatable bladder sutured into the wall of the descending thoracic aorta, a percutaneous access device (PAD) implanted in a hypogastric region of the patient and in fluid communication with the bladder, and a drive unit connectible through the PAD for selectively inflating and deflating the bladder.
US Patent Application Publication 2002/0151761 to Viole et al., which is incorporated herein by reference, describes an intravascular extracardiac system, comprising a pump with inflow and outflow conduits that are implanted intravascularly through a non-primary vessel, and positioned within the patient's vasculature. The pump is configured to be operated continuously or in a pulsatile fashion, synchronous with the patient's heart, thereby potentially reducing the afterload of the heart.
U.S. Pat. No. 3,585,983 to Kantrowitz et al. which is incorporated herein by reference, describes an intra-arterial cardiac-assist device having a balloon which is inflated periodically for diastolic augmentation. U.S. Pat. No. 4,630,597 to Kantrowitz et al., which is incorporated herein by reference, describes a dynamic aortic patch that is permanently surgically implanted in the wall of the aorta to augment the pumping action of the heart. The patch comprises an elongate semi-rigid shell member having a concave inner surface and a flexible membrane integrally bonded to the outer surface of the shell to define an inflatable and deflatable chamber between the concave inner surface and the membrane.
U.S. Pat. No. 4,240,409 to Robinson et al., which is incorporated herein by reference, describes a device for mechanically assisting circulation of blood in a patient for periods of up to two weeks until the patient's heart strengthens sufficiently to take over the full workload. The circulatory assist device includes a valveless pump with a flexible bladder, a pneumatic driver for applying pressure pulses to the bladder, and a single flexible conduit for conveying blood between the patient and the pump. In use, the pump and driver are mounted external to the patient's body and the flexible conduit is connected to the pump and in end-to-side relationship with a major blood vessel on that side of the heart, either right or left, which is in need of support.
U.S. Pat. No. 6,406,422 to Landesberg, which is incorporated herein by reference, describes a ventricular-assist system that utilizes an intraventricular device with a limited volume. The device is expanded at a critical time, for a critical duration, and with a volume change course such that it assists the pumping action of the heart without inducing stretching of the ventricular wall.
U.S. Pat. No. 4,809,676 to Freeman, which is incorporated herein by reference, describes an implantable heart assist device that includes a member to be surgically positioned about the aorta, and a series of electromagnetic segments connected electrically to a source of electricity implanted within or without the body. The electromagnetic segments are C-shaped, and are arranged in pairs. The segments of each pair are positioned opposite to one another in confronting relation surrounding the aorta, and the electrical source is used to energize the segments of each pair to cause the segments to be moved forceably toward one another electromagnetically. Thus, the aorta is squeezed between each pair of segments.
U.S. Pat. No. 4,583,523 to Kleinke et al., which is incorporated herein by reference, describes an implantable heart assist device that includes an elongated assembly extending transversely between the ribs of a person from the rib cage to the aorta of the heart to be assisted. The elongated assembly includes an aorta compressing device at the front end thereof for engaging the aorta externally thereof. A mounting device at the rear end of the elongated assembly supports the device from the ribs of the person, and a motive device actuates and deactivates the compressing means alternatingly to help pump blood through the aorta.
U.S. Pat. No. 4,245,622 to Hutchins, IV, which is incorporated herein by reference, describes an inflatable/deflatable device for use in a body-implantable heart-assist pump. The device includes an inflatable/deflatable central portion, and a noninflatable, generally planar marginal portion joined thereto. In a preferred construction, the device is formed by the marginal joinder of a pair of flexible fluid-impervious sheets, wherein the central portion has opposite sides, and the marginal portion includes stretches distributed along these sides. The two flexible sheets may have different flexibilities, permitting the device to be inflated preferentially in a desired direction, and different curvatures, permitting the device to conform to adjoining surfaces in the heart-assist pump.
US Patent Application 2003/0163020 to Frazier, which is incorporated herein by reference, describes a heart assist system that includes an axial-flow blood pump capable of being implanted in the descending thoracic aorta; a pressure-feedback controller connected to the pump, for controlling the pump, the controller capable of being implanted in the body; and a rechargeable battery pack connected to the pump and to the controller, for providing power to the pump, the battery pack capable of being implanted in the body. A method for assisting a failing heart comprises (a) in response to when a measured dP/dT signal increases during systole, signaling an implanted aortic blood pump to go into a systolic mode and pump blood at a first flow rate; and (b) in response to when the dP/dT signal peaks in the negative region, signaling the pump to go into a diastolic mode and pump blood at a second flow rate.
US Patent Application 2003/0045909 to Gross et al., which is incorporated herein by reference, describes apparatus for treating heart conditions, including an electrode device, which is adapted to be coupled to a vagus nerve of the subject. A control unit is adapted to drive the electrode device to apply to the vagus nerve a stimulating current, which is capable of inducing action potentials in a therapeutic direction in a first set and a second set of nerve fibers of the vagus nerve. The control unit is also adapted to drive the electrode device to apply to the vagus nerve an inhibiting current, which is capable of inhibiting the induced action potentials traveling in the therapeutic direction in the second set of nerve fibers, the nerve fibers in the second set having generally larger diameters than the nerve fibers in the first set.
PCT Publication WO 03/099377 to Ayal et al., which is incorporated herein by reference, describes apparatus for treating a subject, including an electrode device, adapted to be coupled to a vagus nerve of the subject, and a heart rate sensor, configured to detect a heart rate of the subject, and to generate a heart rate signal responsive thereto. The apparatus also includes a control unit, adapted to receive the heart rate signal, and, responsive to determining that the heart rate is greater than a threshold value, which threshold value is greater than a normal heart rate, drive the electrode device to apply a current to the vagus nerve, and configure the current so as to reduce the heart rate of the subject.
“Artificial muscles” are linear actuators that utilize polymers that undergo reversible length changes responsively to electrical or chemical stimuli. Artificial muscles thus convert electrical or chemical energy to mechanical energy. Artificial muscles are well known in the art, and are described for example, in the following patents and publication, all of which are incorporated herein by reference:                U.S. Pat. Nos. 6,545,384 and 6,376,971 to Pelrine et al.;        U.S. Pat. No. 6,223,648 to Erickson;        U.S. Pat. No. 6,586,859 to Kornbluh et al.; and        Brock D L, “Review of artificial muscle based on contractile polymers,” MIT Artificial Intelligence Laboratory, A.I. Memo No. 1330 (November 1991)        
Cell therapy is an approach for repairing and augmenting diseased muscles, such as cardiac muscles. Myogenic cells are cultured and introduced into damaged muscle tissue, such as heart or striated muscle. The myogenic cells fuse with pre-existing muscle cells, transferring into the pre-existing muscle cells the normal genome in their nuclei in order to genetically repair the damaged muscle cells. U.S. Pat. No. 5,130,141 to Law et al., which is incorporated herein by reference, describes compositions for and methods of treating muscle weakness and degeneration. Such compositions include myogenic cells which are administered by the described methods to one or more affected muscles. PCT Publication WO 02/28470 to Law, which is incorporated herein by reference, describes catheters and methods for their use that provide automated delivery of cells to structures in the body such as degenerative or weak muscle.
Gene therapy is the delivery of foreign genes into cells for therapeutic purposes. U.S. Pat. No. 6,297,220 to Leiden et al., which is incorporated herein by reference, describes the use of adenovirus-mediated gene transfer to regulate function in cardiac and vascular smooth muscle cells. A recombinant adenovirus comprising a DNA sequence that codes for a gene product is delivered to a cardiac or vascular smooth muscle cell and the cell is maintained until that gene product is expressed. U.S. Pat. No. 6,100,242 to Hammond et al., which is incorporated herein by reference, describes the use of the transgene-inserted replication-deficit adenovirus vector in in vivo gene therapy for peripheral vascular disease and heart disease, including myocardial ischemia, by a single intra-femoral artery or intracoronary injection directly conducted deeply in the lumen of the one or both femoral or coronary arteries. U.S. Pat. No. 6,306,830 to Hammond et al., which is incorporated herein by reference, describes methods and compositions for enhancing cardiac function by inserting transgenes that increase beta-adrenergic responsiveness within the myocardium. These techniques are described as being useful for the treatment of heart disease, especially congestive heart failure.